# Development of diagnostic and prognostic tests for esophageal adenocarcinoma

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2022 · $240,649

## Abstract

Abstract. The primary goal of this proposal is to develop novel molecular approaches for early detection of
esophageal adenocarcinoma (EAC). EAC arises in the setting of gastroesophageal reflux disease (GERD) and
Barrett's esophagus (BE); a metaplastic change resulting from GERD. This knowledge has driven endoscopic
screening and surveillance recommendations for individuals with GERD and BE but compliance is low and the
vast majority of new EAC cases are still diagnosed at late stage, when the tumor is inoperable and prognosis is
extremely poor. Over the past 6-8 years, we have developed a highly collaborative, multi-institutional and multi-
disciplinary team focused on the development of clinically useful biomarkers for EAC. This proposal will build
on our previously funded projects and the clinical and technical resources available to us through these
studies, in order to evaluate two different approaches to early detection of EAC. The first approach is based on
detection of somatic mutation and DNA copy number abnormality signatures in esophageal cytology samples.
Published studies and our own ongoing work strongly indicate that accumulation of somatic mutations and
major chromosomal rearrangements drive the progression from BE to EAC. We believe that these changes
can be leveraged to identify a genomic signature for progression that can be detected in cytology samples
using a targeted next-generation sequencing (NGS) test. Identification of the genomic signature is ongoing in
our group through large-scale comparative sequencing of EAC and pre-neoplastic tissue samples. To evaluate
the effectiveness of this signature in identifying progression, we are currently collecting ~350 esophageal
cytology samples using an encapsulated sponge called the EsophaCap™. This device is not yet commercially
available, but has been provided to us under arrangement with CapNostics LLC and is currently approved for
investigational testing in the USA and Canada. These unique data and tissue resources will be used in Specific
Aim 1 to evaluate the sensitivity and specificity of a targeted NGS analysis of esophageal cytology samples to
detect dysplasia and early EAC. The second approach also leverages our large-scale sequencing data and
targeted sequencing assays, but in this case we will evaluate the detection of mutations in circulating, cell-free
DNA isolated from plasma as a biomarker for EAC. We are currently collecting plasma from all patients who
swallow the EsophaCap™ device and this provides an excellent tissue resource in which to test detection of
circulating tumor DNA (ctDNA). To aid in the detection of ctDNA, we have developed an ultra-sensitive NGS-
based assay that can detect mutations at multiple loci with sensitivity as low as 0.05% (1/2000) mutant allele
fraction. These resources will be used in Specific Aim 2 in order to evaluate the sensitivity and specificity of
ctDNA for detection of stage I and II EAC. Finally, studies indicate that ctDNA dete...

## Key facts

- **NIH application ID:** 10308014
- **Project number:** 5R01CA208599-06
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Tony E Godfrey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $240,649
- **Award type:** 5
- **Project period:** 2016-12-16 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10308014

## Citation

> US National Institutes of Health, RePORTER application 10308014, Development of diagnostic and prognostic tests for esophageal adenocarcinoma (5R01CA208599-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10308014. Licensed CC0.

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